Megakaryopoiesis and thrombopoiesis. HSCs reside in the BM osteoblastic niche and differentiate into MK progenitors and finally into mature polyploidy MKs. This process, called megakaryopoiesis, includes endomitotic cell cycles, leading to polyploidy and markedly enlarged cell size. TPO is the primary regulator of megakaryopoiesis, inducing differentiation and maturation of MKs. In the osteoblastic niche, collagen I inhibits platelet production through interaction with the MK integrin α2β1. Platelet production is dependent on MKs migration toward the vascular niche, where they interact with sinusoidal endothelial cells, produce long-branching transendothelial extensions called proplatelets, and release platelets into the circulation. Migration and localization of MKs in proximity to the BM sinusoids is regulated by several factors, among which the chemokine CXCL12 and its receptor CXCR4 that increase mobility of MK progenitors, facilitating their interaction with sinusoidal endothelial cells mediated by endothelial cell vascular cell adhesion molecule-1 and MK integrin α4β1.